INERT METAL ION PROTECTING GROUPS IN PEPTIDE SYNTHESIS

肽合成中的惰性金属离子保护基团

• 批准号: 3273812
• 负责人: STEPHAN S. ISIED
• 金额: $ 8.84万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3273812
• 关键词: aminoacid analog; angiotensin II; drug design /synthesis /production; metal complex; oxidation reduction reaction; peptides; protective chemical group; racemization

Synthetic peptide methods share in common the protection of amino acid terminals and side chains to help direct peptide formation. During peptide synthesis the properties of these protecting groups become vital to the success of the synthesis. Some of these protecting groups render peptide fragments insoluble and therefore limit the synthesis. Metal ion protecting groups are proposed to replace and complement other organic groups. Attractive features of metal ions include their charge, color, and ease of introduction and removal. The positive charge of the metal ion protecting group can be a handle which will significantly aid in the purification of the synthesized peptide at any stage during the synthesis. Kinetically inert metal ions can be as stable as organic protecting groups, yet can be easily removed under very mild conditions (by making use of their redox properties). We are proposing to use kinetically inert metal ions, especially ((NH3)5Co(III)-) and other cobalt (III) derivatives, to aid peptide synthesis in a variety of ways: (a) as a protecting group for C-and N-terminals; (b) as a protecting group for various amino acid side chains; (c) the incorporation of cobalt(III) onto a polymeric support is suggested to allow the removal of a peptide from the polymeric support under very mild conditions; and finally, (d) the subject of peptide synthesis in aqueous solution is approached using these water soluble metal ion protecting groups which can be removed under very mild conditions. Angiotensin II, an eight residue polypeptide, will be synthesized using cobalt(III) protecting groups to demonstrate the usefulness of this approach.

合成肽方法的共同点是氨基酸末端的保护 和侧链帮助指导肽的形成。 在肽合成过程中 这些保护基团的特性对成功至关重要 合成。 其中一些保护基团使肽片段不溶 从而限制了合成。 建议使用金属离子保护基团来替代和补充其他有机基团 组。 金属离子的吸引人的特征包括它们的电荷、颜色和易用性 的引入和删除。 金属离子的正电荷保护 基团可以是一个手柄，它将极大地帮助纯化 在合成过程中的任何阶段合成肽。 动力学惰性金属 离子可以像有机保护基团一样稳定，但可以轻松去除 在非常温和的条件下（通过利用其氧化还原特性）。 我们建议使用动力学惰性金属离子，特别是 ((NH3)5Co(III)-) 和其他钴 (III) 衍生物，有助于肽合成 有多种方式：(a) 作为 C 端和 N 端的保护基； (b) 作为 各种氨基酸侧链的保护基； (c) 纳入 建议将钴（III）附着在聚合物载体上，以去除 在非常温和的条件下从聚合物支持物中提取肽；最后，(d) 使用这些方法来研究水溶液中肽合成的主题 水溶性金属离子保护基团，可在非常温和的条件下去除 状况。 血管紧张素 II 是一种八残基多肽，将使用以下方法合成 钴（III）保护基团以证明该方法的有用性。